Management of the upper extremity in juvenile rheumatoid arthritis

Juvenile rheumatoid arthritis is a multifaceted disease. Average age of onset is 6 years, with peaks between 1 and 4 and between 9 and 14 years. Girls are affected more frequently than boys. Nonsteroidal anti-inflammatory drugs are the standard first line of therapy. Second-line therapy of antirheumatic drugs may be used early for progressive disease. Intra-articular corticosteroid injections should be considered to preserve joint mobility and muscle strength when medical treatment fails to control synovitis or when marked functional impairment exists. Historically, surgery has been a last resort, but in appropriate patients, it should be considered soon after failure of conservative management. However, when possible, reconstructive surgery should be delayed until completion of skeletal growth.     

Release of synenkephalin from neuronal terminals in vitro

Synenkephalin, the amino-terminal 1-70 residues of proenkephalin is released intact from bovine globus pallidus following potassium-induced depolarization in vitro via a Ca++ dependent mechanism. The release of synenkephalin accompanies that of Met-enkephalin in a molar ratio of 1/4. In contrast to Met-enkephalin which is readily destroyed when released, synenkephalin is not destroyed.     

Electrophysiological correlates of anticipatory task-switching processes

Recent studies show a differential switch-related positivity emerging before a switch trial and reflecting anticipatory task-set reconfiguration processes. In this study, the switch-related positivity was examined in a cued task-switching paradigm. Cue-stimulus and response-stimulus intervals were independently manipulated to dissociate between the effects of anticipatory preparation and passive dissipation of task-set interference. Reaction time switch cost declined with increasing cue-stimulus and response-stimulus intervals, suggesting a contribution from both active preparation and passive interference processes. In cue-related difference waveforms, a switch positivity peaked around 350-400 ms and is interpreted as reflecting differential activation of task-set reconfiguration. In stimulus-related difference waveforms, a switch-related negativity is believed to indicate the role of S-R priming and response interference in task-switching.     

The Italian Group for LAP-BAND: predictive value of initial body mass index for weight loss after 5 years of follow-up

Background Laparoscopic of the LAP-BAND System placement stage of obesity is a safe operation, but its indication in terms of stage of obesity is controversial. The aim of this study was to evaluate the 5 years stage of obesity results for weight loss in patients with varying preoperative ranges of body mass index (BMI).Methods Data were obtained from the Italian Collaborative Study Group for LAP-BAND System (GILB) registry. Detailed information was collected on a specifically created database (MS Access 2000) for patients operated on in Italy from January 1996 to 2003. Patients operated on between January 1996 and December 1997 were allocated to four groups according to preoperative BMI range: 30–39.9 kg/m² (group A), 40–49.9 kg/m² (group B), 50–59.9 kg/m² (group C), and =60 kg/m² (group D) percent estimated weight loss respectively. Postoperative complications, mortality, BMI, BMI loss, and (%EWL) were considered in each group. Data are expressed as mean ± SD, except as otherwise indicated. Statistical analysis was done by means of Fishers exact test, and p < 0.05 was considered significant.Results After 5 years from LAP-BAND System surgery, 573 of 3,562 patients were eligible for the study. One hundred fifty-five of 573 (27.0%) were lost to follow-up, 24 of 418 (5.7%) underwent band removal due to complications (gastric pouch dilation, band erosion), eight of 418 (1.9%) were converted to other bariatric procedures, five of 418 (1.2%) died of causes not related to the operation or the band, and 381 of 573 (66.5%) were available for follow-up. Based on 96, 214, 64, and seven patients their preoperative BMI, Were allocated to groups A, B, C, and D, respectively. At time of follow-up mean BMI was 27.5 ± 5.2 in group A, 31.6 ± 4.7 in group B, 37.6 ± 17.3 in group C, and 41.4 ± 6.9 kg/m² in group D. Mean BMI loss was 9.8 ± 5.4, 12.9 ± 5.2, 15.8 ± 8.1, and 23.2 ± 4.9 kg/m², respectively, in groups A, B, C, and D. Mean %EWL at the same time was 54.6 ± 32.3 in group A, 54.1 ± 17.2 in group B, 51.6 ± 35 in group C, and 59.l ± 17.1 in group D.Conclusion Initial BMI in this series did not correlate with %EWL 5 years after the operation. In fact %EWL was almost the same in each group, independent of preoperative weight. Initial BMI was an accurate indicator of the results obtained 5 years after LAP-BAND in group C (50–59.9 kg/m²) and D (=60 kg/m²) patients, who remained morbidly obese despite their %EWL.     

Hydrophobic vancomycin derivatives with improved ADME properties: discovery of telavancin (TD-6424)

Novel derivatives of N-decylaminoethylvancomycin (2), containing appended hydrophilic groups were synthesized and their antibacterial activity and ADME properties were evaluated. The compounds were prepared by reacting amines with the C-terminus (C-) of 2 using PyBOP mediated amide formation, or with the resorcinol-like (R-) position of 2 using a Mannich aminomethylation reaction. These analogs retained the antibacterial activity of 2 against methicillin-resistant staphylococci and vancomycin-resistant enterococci. Compounds with a negatively charged auxiliary group also exhibited improved ADME properties relative to 2. In particular, R-phosphonomethylaminomethyl derivative 21 displayed good in vitro antibacterial activity, high urinary recovery and low distribution to liver and kidney tissues. Based on these results, 21 was advanced into development as TD-6424, and is currently in human clinical trials. The generic name telavancin has recently been approved for compound 21.     

Breast density as a determinant of interval cancer at mammographic screening

The association of breast density (% of breast volume involved by fibro-glandular densities) with the risk of interval cancer (IC) was investigated by reviewing a consecutive series of 346 cancers detected at screening (SDC) during 1996-1999 and of 90 ICs, reported as negative in the same period and diagnosed in the following 2 years, and comparing them to a random sample of 360 healthy controls. The probability of IC was significantly associated with breast density, whatever grouping (0/1-25/26-74/>74%; 0-25/26-60/61-74/>74%; 0-25/26-74/>74%) was considered (chi(2)=30.67-34.08, P<0.<0.01): 27.8% of all ICs were classified in the >74% density class, as compared to 7% of SDC and 5% of healthy controls. No significant association to IC was observed for Wolfe pattern (P2/Dy vs N1/P1: chi(2)=0.30, P=0.960), number of used mammographic views (single oblique vs oblique+craniocaudal: chi(2)=0.02, P=0.90) or screening round (first vs repeat: chi(2)=1.41, P=0.23). Multivariate analysis confirmed the independent association of breast density to IC, the highest risk being observed for >74% density class (OR vs 0% class=13.4, 95% CI 2.7-65.6, OR vs all other density classes=5.1, 95% CI 2.6-10.0). Age showed an independent association too, older women having a lower risk of IC (OR=0.52 95% CI 0.3-09). Breast density (>74%) resulted as being a major determinant of IC. Special screening protocols (shorter rescreening interval, routine use of ultrasonography) might be suggested for these subjects in order to improve screening sensitivity and efficacy.     

Breast cancer mortality trends in two areas of the province of Florence, Italy, where screening programmes started in the 1970s and 1990s

We compared breast cancer mortality rates in the period 1985-2000 in two areas of the province of Florence, Italy, where breast cancer screening programmes started in the 1970s (early screening (ES) area) and in 1990s (late screening (LS) area). The overall age-standardised mortality decreased in the whole period by 40.9% in the ES area (P<0.001), and by 11.3% in the LS area (P=0.030). Significant decreases in the ES area were detected in groups aged 45-54 years (61.1%; P= 0.018) and 65-74 years (44.7%; P= 0.049), whereas in the LS area no significant decrease was detected in any age group. The relatively low compliance in the first years of the programme in both areas, and the long enrollment period in the LS area could have reduced the effect on mortality. Our findings suggest that the drop in mortality in the ES area (41%) could be explained by both service screening and better care. The slight decrease in mortality in the LS area (11%) could be mainly due to better care. A reduction of about 30% is attributable to screening in the ES area over the period 1985-2000.     

Increasing trends of cervical adenocarcinoma incidence in Central Italy despite Extensive Screening Programme, 1985-2000

Incidence rates of adenocarcinoma of the uterine cervix have been reported to be increasing in several countries, but not in Italy. The aim of the present study was to analyse trends in cervical cancer incidence by histological type in two districts of Central Italy (Florence and Prato), covered by the Tuscany Cancer Registry (RTT), where cytological screening had been available since the 1970s. Incident cervical cancers during 1985-2000 were 1012. Estimated Annual Percent Change (EAPC) by age-groups and histological type were computed. Incidence increased for adenocarcinoma (EAPC = +5.7%; 95% confidence interval (CI)+2.8; +8.6); whereas, it decreased for squamous cancer (EAPC = -1.9%; 95% CI-3.8; 0) and for other or not specified types (EAPC = -4.4%; 95% CI-10.0; +1.5). Adenocarcinoma increased significantly among younger women (<55 years) but not among older ones, whereas squamous cell cancer decreased among older women only. The burden of cervical cancers might increase in the future if no specific preventive strategies for adenocarcinoma are implemented.     

Microscopic imaging of extended tissue volumes

1. Detailed information about three-dimensional structure is key to understanding biological function. 2. Confocal laser microscopy has made it possible to reconstruct three-dimensional organization with exquisite resolution at cellular and subcellular levels. 3. There have been few attempts to acquire large image volumes using the confocal laser scanning microscope. 4. Previously, we have used manual techniques to construct extended volumes (several mm in extent, at 1.5 microm voxel size) of myocardial tissue. 5. We are now developing equipment and efficient automated methods for acquiring extended morphometric databases using confocal laser scanning microscopy.